Background: There are limited data on incidence of CMV reactivation and safety of anti-CMV prophylaxis in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. We aimed to describe the rate of CMV viremia in patients receiving two different prophylaxis regimens based on risk assessment. The frequency of toxicity from prophylaxis is also reported.
Methods: We assembled a single center cohort of allogeneic HCT recipients undergoing CMV surveillance testing between January 1, 2014 to June 30, 2017. Subjects were excluded if they were CMV PCR positive in the 30 days prior to HCT. Patients were categorized as high-risk (HR) if the donor product was from a CMV positive patient and they met one of the following criteria: T cell depleted graft, cord blood transplant, or receipt of anti-thymocyte globulin or alemtuzumab. The local CMV prophylaxis pathway recommends all patients initiate standard dose acyclovir on day -7. HR patients transition to foscarnet in the first week post-transplant which is continued until enteral therapy is tolerated. They are then transitioned to valganciclovir, which is continued through day +100. Standard-risk (SR) patients continue acyclovir through day +100. Patients were followed until day +180 for these outcomes: CMV viremia, CMV disease, and CMV prophylaxis related-toxicity.
Results: The cohort included 147 subjects with 44 developing CMV viremia (29.9%). CMV viremia was more common in HR (18/35) as compared to SR (26/112) patients (51.4 vs. 23.2%, p<0.01). The median time to reactivation was also earlier in HR patients (9 vs. 33.5 days, p=0.01). Only two (4.5%) patients with CMV viremia progressed to CMV disease. Toxicity requiring a therapeutic change of an antiviral prophylactic agent was more common in HR (25.7%) versus SR (8.9%) patients. Renal insufficiency was the most common reported toxicity, followed by electrolyte wasting (figure).
Conclusion: HR HCT recipients had a CMV viremia rate nearly triple the SR group despite a more comprehensive prophylaxis regimen. Few subjects with CMV viremia progressed to CMV disease but toxicities from antiviral prophylaxis were common. Further investigations of novel CMV prophylaxis agents with improved toxicity profile are needed to justify CMV prophylaxis in pediatric HCT patients.
C. L. K. Boge, Merck: Grant Investigator , Research grant .
J. Freedman, None
B. T. Fisher, Merck: Grant Investigator , Grant recipient and Research grant .